Enhanced Adenovirus Vaccine Safety Surveillance in Military Setting, United States

The US Coast Guard Academy began adenovirus vaccination of incoming cadets in 2022. Of 294 vaccine recipients, 15%–20% had mild respiratory or systemic symptoms within 10 days postvaccination but no serious adverse events after 90 days. Our findings support the continued use of adenovirus vaccines in congregate military settings.

A denovirus infection results in considerable illness among congregate military populations (1). US Food and Drug Administration-approved use of a live, oral, bivalent adenovirus vaccine for military populations began in 2011 and was associated with substantial decreases in adenovirus infection incidence at US military basic training centers (2,3). The US Naval Academy introduced adenovirus vaccination in 2018 after a large adenovirus outbreak (4). An adenovirus outbreak involving ≈300 cadets occurred at the US Coast Guard Academy (CGA) in 2019 (5). Adenovirus vaccines were introduced for incoming first-year CGA cadets on June 28, 2022. To supplement postlicensure data on adenovirus vaccine safety (6), we monitored postvaccination signs and symptoms in those cadets.
We developed a monitoring system to account for military training features, such as restricted cellphone access and a time-sensitive, regimented curriculum. For sick call visits occurring <10 days after vaccination, the CGA clinic used a monitoring tool (Appendix, https://wwwnc.cdc.gov/EID/article/29/6/23-0331-App1.pdf) consisting of 17 postvaccination signs or symptoms obtained from clinical trial results (7,8). We measured vaccine uptake and inability to swallow pills and monitored cadets for 90 days after vaccination for US Food and Drug Administrationdefined serious adverse events (9).
Cadets received an in-person briefing from CGA clinic staff on June 27, 2022. The CGA training cadre, with whom the cadets had daily contact, were briefed by clinic leadership on the paper-based reporting tool, reporting requirements, and referring ill cadets to the CGA clinic. Before vaccination, cadets were given the Centers for Disease Control and Prevention adenovirus vaccine information statement and opportunity to ask questions. Subsequently, if cadets sought care for illness at the CGA clinic, staff used the reporting tool to record whether any of the 17 signs and symptoms were present.
The US Coast Guard Academy began adenovirus vaccination of incoming cadets in 2022. Of 294 vaccine recipients, 15%-20% had mild respiratory or systemic symptoms within 10 days postvaccination but no serious adverse events after 90 days. Our findings support the continued use of adenovirus vaccines in congregate military settings.
During the enhanced postimmunization monitoring period, a concomitant COVID-19 outbreak affected ≈20% of first-year cadets. Of the 65 students who sought care at the CGA clinic and had >1 enhanced surveillance sign or symptom, 8 (12.3%) also tested positive for COVID-19.
The live adenovirus vaccine was well-tolerated; only 4 vaccination failures occurred, the cadets who could not swallow the medication. Of 294 vaccinated CGA cadets, <25% reported signs or symptoms during the monitoring period. Phase 1 adenovirus vaccine trial data (7) showed symptom occurrence reached 33% within 8 weeks postvaccination. The most common signs and symptoms reported among CGA firstyear cadets corresponded with those noted in a large phase 3 adenovirus trial (8), including headache, sore throat, nasal congestion, and cough. In this cohort, rates for gastrointestinal symptoms (2.3%-8.3%) were lower than those reported in the phase 3 trial (8).
Shortness of breath in 11.6% of cadets did not clearly correspond to signs and symptoms identified in phase 1 or phase 3 trial safety data. Given that >25% of nonhospitalized adults with COVID-19 report shortness of breath (10), the concurrent COV-ID-19 outbreak might have contributed to reports of this specific symptom.
In conclusion, enhanced passive monitoring established after introducing adenovirus vaccination for incoming first-year CGA cadets did not identify any serious adverse events. Even with the receipt of multiple vaccines and an intercurrent COVID-19 outbreak, the signs and symptoms profile among cadets who had sick calls during the 10-day postvaccination period appears consistent with profiles reported in previous adenovirus vaccine trials. A positive CO-VID-19 test was observed for 12.3% of cadets who completed the surveillance questionnaire during their sick call, which might explain the 11.6% of cadets who reported shortness of breath. Our favorable real-world findings support continuing adenovirus vaccination of incoming CGA cadet classes and wider use of the vaccine in congregate military settings. W e report a case of ocular-only mpox infection in a 53-year-old man in San Francisco, California, USA. His medical history included chronic lymphocytic leukemia (CLL), inactive 2 years after treatment with obinutuzumab and venetoclax but with persistent lymphopenia. He reported male sexual partners but was HIV negative. Symptoms in his right eye began August 2022 as itching and nasal scleral redness (Figure, panel A). There was no fever, rash, or lymphadenopathy. Eye redness worsened; the patient sought care at an urgent care facility and was given erythromycin ointment. Continued vision loss led to an emergency department visit, resulting in a diagnosis of preseptal cellulitis, treated with trimethoprim/ sulfamethoxazole plus amoxicillin/clavulanic acid.
In early September 2022, the patient sought care at a county eye clinic for purulent conjunctivitis and corneal epithelial defects. Clinicians suspected gonococcal conjunctivitis and administered intramuscular ceftriaxone and topical moxifloxacin 0.5%. Bacterial and fungal ocular cultures and herpetic viral PCR returned negative results. Topical prednisolone acetate 1% and oral valacyclovir failed to control the eye inflammation. Three weeks after initial symptoms appeared, the patient's ocular inflammation increased; keratic precipitates and a moderate corneal opacity developed. Uveitis and scleritis workups did not yield a specific diagnosis (Table).
In late September 2022, at a second opinion examination at a University of California clinic, the patient's right eye acuity was 20/640. Examination showed a nasal patch of avascular scleral necrosis ( Figure, panel B), and corneal epithelial sloughing (Figure, panel C) with microcystic edema. Repeat ocular surface cultures and PCR were negative. Given the negative results of extensive infectious etiology testing, we prescribed oral prednisone (40 mg/d) for presumed undifferentiated necrotizing anterior scleritis and keratitis.
One week later, corneal inflammation worsened (Figure, panel D). Clinical deterioration on systemic steroids continued to raise suspicion for ocular infection; we stopped steroid treatments. Again, cultures and PCR remained negative. Without prednisone, the patient's limbal infiltrates worsened, with progressive corneal haze. White corneal endothelial plaques appeared. We performed anterior chamber paracentesis for cultures, viral PCR, and an RNA deep-sequencing (RNA-seq) protocol previously described (1). The patient's scleritis, keratitis, and anterior uveitis worsened (Figure, panels E, F). Right eye vision decreased to hand motion only. We performed a diagnostic scleral and corneal biopsy and initiated We report a case of a 53-year-old HIV-negative patient in San Francisco, California, USA, with no classic mpox prodromal symptoms or skin lesions who experienced fulminant, vision-threatening scleritis, keratitis, and uveitis. Deep sequence analysis identified monkeypox virus RNA in the aqueous humor. We confirmed the virus on the cornea and sclera by PCR.